1. Field of the Invention
The present invention relates generally to apparatus and methods for treating atherosclerotic disease. In a particular embodiment, the present invention provides a combination of controlled cryogenic cooling and balloon distention of a diseased vessel wall.
A number of percutaneous intravascular procedures have been developed for treating atherosclerotic disease in a patient""s vasculature. The most successful of these treatments is percutaneous transluminal angioplasty (PTA). PTA employs a catheter having an expansible distal end (usually in the form of an inflatable balloon) to dilate a stenotic region in the vasculature to restore adequate blood flow beyond the stenosis. Other procedures for opening stenotic regions include directional arthrectlomy, rotational arthrectomy, laser angioplasty, stenting, and the like. While these procedures have gained wide acceptance (either alone or in combination, particularly PTA in combination with stenting), they continue to suffer from significant disadvantages. A particularly common disadvantage with PTA and other known procedures for opening stenotic regions is the subsequent occurrence of restenosis.
Restenosis refers to the re-narrowing of an artery following an initially successful angioplasty or other primary treatment. Restenosis typically occurs within weeks or months of the primary procedure, and may affect up to 50% of all angioplasty patients to some extent. Restenosis results at least in part from smooth muscle cell proliferation in response to the injury caused by the primary treatment. This cell proliferation is referred to as xe2x80x9chyperplasia.xe2x80x9d Blood vessels in which significant restenosis occurs will typically require further treatment.
A number of strategies have been proposed to treat hyperplasia and reduce restenosis. Previously proposed strategies include prolonged balloon inflation, treatment of the blood vessel with a heated balloon, treatment of the blood vessel with radiation, the administration of anti-thrombotic dnigs following the primary treatment, stenting of the region following the primary treatment, and the like. While these proposals have enjoyed varying levels of success, no one of these procedures is proven to be entirely successful in avoiding all occurrences of restenosis and hyperplasia.
It has recently been proposed to prevent or slow reclosure of a lesion following angioplasty by remodeling the lesion using a combination of dilation and cryogenic cooling. Co-pending U.S. patent application Ser. No. 09/203,011, filed Dec. 1, 1998 , the full disclosure of which is incorporated herein by reference, describes an exemplary structure and method for inhibiting restenosis using a cryogenically cooled balloon. While these proposals appear promising, the described structures and methods for carrying out endovascular cryogenic cooling would benefit from still further refinements and improvements.
In light of the above, it would be desirable to provide improved devices, system, and methods for treatment of diseased blood vessels. It would be further desirable if these improved techniques were compatible with known methlods for treating atherosclerotic disease, but reduced the actual occurrence and/or extent o f restenosis due to hyperplasia. It would be particularly desirable if these improved techniques were capable of delivering treatment in a very safe and controlled manner so as to avoid injury to adjacent tissues. These devices, systems, and methods should ideally also inhibit hyperplasia and/or neoplasia in the target tissue with minimum side effects, and without requiring a complex control system or making a physician introduce numerous different treatment structures into the target area. At least some of these objections will be met by the invention described hereinafter.
2. Description of the Background Art
A cryoplasty device and method are described in WO 98/38934. Balloon catheters for intravascular cooling or heating of a patient are described in U.S. Pat. No. 5,486,208 and WO 91/05528. A cryosurgical probe with an inflatable bladder for performing intrauterine ablation is described in U.S. Pat. No. 5,501,681. Cryosurgical probes relying on Joule-Thomson cooling are described in U.S. Pat. Nos. 5,275,595; 5,190,539; 5,147,355; 5,078,713; and 3,901,241. Catheters with heated balloons for post-angioplasty and other treatments are described in U.S. Pat. Nos. 5, 196,024; 5,191,883; 5,151,100; 5,106,360; 5,092,841; 5,041,089; 5,019,075; and 4,754,752. Cryogenic fluid sources are described in U.S. Pat. Nos. 5,644,502; 5,6 117,739; and 4,336,691. The following U.S. Patents may also be relevant to the present invention: U.S. Pat. Nos. 5,458,612; 5,545,195; 5,733,280; 5,902,299; and 5,868,735. The full disclosures of each of the above U.S. patents are incorporated by reference.
The present invention provides new techniques for treating atherosclerotic disease using controlled cryogenic cooling. The invention may make use of a combination cryogenic/angioplasty catheter, eliminating any need for an exchange procedure to be preformed between dilation of a stenotic region within a vessel wall and the application of cryogenic cooling to inhibit hyperplasia. The cooling catheter may be suitable for cooling the diseased blood vessel before, during, and/or after dilation. Advantageously, controlled cooling of the vessel wall changes its mechanical properties so as to enhance the ease of concurrent and/or subsequent dilation. More specifically, the cooling process may weaken the vessel and allows it to be expanded with a much lower balloon pressure than with conventional uncooled angioplasty. Controlled cooling of the vessel wall has been found to effectively reduce actual and/or observed hyperplasia as compared to conventional uncooled treatment of the blood vessel. Reductions in restenosis may be provided for primary treatments of the blood vessel including angioplasty, directional arthrectomy, rotational arthrectomy, laser angioplasty, stenting, and the like. Cooling of the vessel wall will often be performed through plaque, and the cooling process will preferably take the thermodynamic effects of the plaque into account so as to enhance efficacy while inhibiting morbidity.
In a first aspect, the present invention provides a method for treating hyperplasia or neoplasia of a blood vessel region. The method comprises cooling an inner surface of the blood vessel region to a temperature and for a time sufficient to remodel the blood vessel such that observed subsequent excessive cell growth-induced stenosis of the blood vessel is reduced as compared to a stenosis of an equivalently treated uncooled blood vessel region.
Typically, the cooling will reduce stenosis by a relative amount of at least about 5% of the stenosis which would otherwise occur in the vessel, preferably by at least about 10%, and more preferably by at least about 25%. Ideally, the cooling step effects a relative reduction of the stenosis of it least about 50% of the equivalent vessel region stenosis, and may even be tailored to reduce stenosis by about 80% or more. Measured reductions in absolute stenosis percentages often measure more than 6%, preferably being more than 8%, and in experiments described herein, have been shown to be more than 15% and even better than 22%. Such benefits are provided by cooling times in a range from about 10 to about 30 seconds, and with the cooling temperature of the inner surface of the blood vessel being in a range from about 4xc2x0 to about xe2x88x9231xc2x0 C. (preferably being in a range from about xe2x88x925xc2x0 to about xe2x88x9215xc2x0 C.).
In another aspect, the invention provides a method for inhibiting restenosis of a blood vessel region of a mammal. The blood vessel region is subjected to a primary treatment effecting an initial reduction in stenosis and inducing the restenosis. Typical primary treatments include directional angioplasty, arthrectomy, rotational arthrectomy, laser angioplasty, stenting, and the like. The method comprises cooling an inner surface of the blood vessel region to a temperature and for a time sufficient to remodel the blood vessel region such that observed restenosis of the blood vessel is measurably inhibited. Typically, the cooling step induces at least one of apoptosis, cell membrane damage, and programmed cell death so as to provide these advantages.
In another aspect, the invention provides a method for inhibiting restenosis of a blood vessel region. The blood vessel region is subjected to a primary treatment effecting an initial reduction in stenosis and inducing the restenosis. The method comprises cooling an inner surface of the blood vessel region, and then reducing cooling so that the inner surface of the blood vessel warms. The warmed inner surface is re-cooled so as to define at least one cooling/warming/cooling cycle. The at least one cycle has cooling temperatures and cooling times sufficient to remodel the blood vessel region such that the restenosis of the blood vessel is measurably inhibited
In another aspect, the invention provides a method for treating a blood vessel. The blood vessel has plaque disposed between a lumen and a vessel wall of tissue. The method comprises cooling the vessel wall tissue to a temperature sufficient to inhibit excessive subsequent cell growth-induced stenosis of the blood vessel. This cooling step is performed by engaging a surface of the plaque with a cooling surface, and cooling the plaque with the cooling surface so that the plaque cools the vessel wall tissue.
Preferably, the vessel wall tissue will be cooled to a target temperature in the range from about xe2x88x924xc2x0 C. to about xe2x88x9215xc2x0 C. It should be noted that the cooling surface will often cool the lesion to a temperature significantly below that of the target temperature, as a significant thermogradient may exist between an inner surface of the plaque and a plaque/endothelial tissue interface. In fact, the cooling surface may cool the plaque to a temperature below the xe2x88x925xc2x0 C. to xe2x88x9215xc2x0 C. range.
In many embodiments, the vessel wall may be cooled to the target temperature for less than about 20 seconds, typically being cooled for at lest about 10 seconds. A rate of change of temperature of the vessel wall tissue may be significantly less than a rate of change of a plaque surface temperature, again in recognition of the thermodynamic effects of the plaque. Hence, in part because the presence of the plaque, the vessel wall tissue may stay at a reduced temperature for a significant amount of time after cooling is terminated. In general, at least one of the characteristics of the cooling process, such as a temperature of the cooling surface and/or a cooling time, may be determined at least in part based on a thickness of the plaque, as the plaque may have a surprisingly large impact on the cooling regimen to provide the desired tissue temperature cycle.